Seeking a cure for muscular dystrophy

Edmonton team closing in on effective treatment for two devastating genetic diseases

Exon skipping. DNA stitches. DNA-like cocktails. Molecular Band-aids.

You might think you’re in Sickbay on the Starship Enterprise when you hear these terms. But they are the novel therapies Toshifumi Yokota and his team are researching in an Edmonton laboratory as they work toward a treatment and hopefully a cure someday for two of the most devastating genetic diseases affecting children.

Yokota, who was recruited to the University of Alberta in 2011 for a new Friends of Garrett Cumming Muscular Dystrophy Research Chair, believes he and his team are close to optimizing a promising new therapy for Duchenne muscular dystrophy, the most common and lethal genetic disorder in childhood. One in every 3,500 to 5,000 boys is born with Duchenne muscular dystrophy. They rarely live beyond their 20s or 30s.

The team is doing similar research into a treatment for another genetic disease called spinal muscular atrophy (SMA), a neurogenic disorder that is the most common cause of infant death worldwide.

“We are working on a new concept that people could not even have imagined 10 or 20 years ago,” says Yokota.

Duchenne muscular dystrophy is an inherited disorder caused by a gene mutation that interferes with the production of proteins called dystrophin, which are needed to form healthy muscles. Signs of muscle weakness are usually seen when the boys are between three and five. Most need a wheelchair by age 12.

In recent years, Duchenne muscular dystrophy researchers have developed a promising molecular treatment called exon skipping, in which synthetic chemicals known as DNA-like molecules are used to improve how cells produce and restore proteins. Yokota’s previous studies led to the development of one such molecule called viltolarsen, which was approved in Japan in 2020 and is currently under review for FDA approval. A few of these DNA-like molecules have been approved by the U.S. Food and Drug Administration and there have been some clinical trials, but the results have not been as positive as hoped.

That’s where Yokota and his team come in. They are working on developing better combinations of these DNA-like molecules that are more effective and with fewer side effects. They are also developing new ways of improving the delivery of these molecules to the muscles of Duchenne muscular dystrophy patients. In laboratory studies on mice and in human cells, they have already demonstrated that their cocktail of DNA-like molecules has effectively restored protein production to keep muscles healthy.

“We are getting closer,” says Yokota. His team of 10 researchers, graduate and undergraduate students has filed several patents and they are working with a U.S. company to move their research forward toward clinical trials. Yokota hopes those will happen within several years.

His research at the University of Alberta could not have happened without the financial help of WCHRI and the Stollery Children’s Hospital Foundation. They have supported the team with innovation grants, student funding and graduate scholarships totalling almost $300,000. “WCHRI is very important to us, especially because it’s currently very difficult to get federal funding,” says Yokota.

He is hopeful that his research will lead to a treatment and eventually a cure for Duchenne muscular dystrophy. “We want both,” he stresses. “We are looking for a cure but I don’t think it’s very likely in the short term.

“Exon skipping drugs approved last few years can only slow down the symptoms. Hopefully, we can develop more optimized ones which can improve symptoms in Duchenne muscular dystrophy patients within five or 10 years.”

Yokota was supported by the Stollery Children’s Hospital Foundation through WCHRI.

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